The COVID-19 pandemic, along with the neurological complications seen in long COVID patients, has brought renewed attention to the possible link between viral infections and neurodegenerative diseases. Although viruses like herpes simplex virus 1 (HSV-1) are known to infect the central nervous system (CNS), causing acute or chronic conditions, the absence of a clear mechanism connecting viral infections with the protein aggregation characteristic of neurodegeneration has long puzzled researchers.
In a recent study, it was demonstrated that viruses can initiate amyloid aggregation in proteins through a direct physicochemical process called heterogeneous nucleation (HEN). When HSV-1 and SARS-CoV-2 were incubated with human cerebrospinal fluid (CSF), amyloid aggregation occurred in several proteins associated with neurodegenerative diseases, including:
🔮 APLP1 (amyloid beta precursor-like protein 1)
🔮 ApoE
🔮 Clusterin
🔮 α2-macroglobulin
🔮 PGK-1 (phosphoglycerate kinase 1)
🔮 Ceruloplasmin
🔮 Nucleolin
🔮 14-3-3
🔮 Transthyretin
🔮 Vitronectin
It was also shown that UV-inactivation of SARS-CoV-2 did not impact its ability to induce amyloid aggregation, suggesting that the process is driven by viral surface catalysis via HEN rather than viral replication. Furthermore, this viral-induced amyloid aggregation led to a significant reduction in the soluble protein concentration in CSF.
These findings offer a possible explanation for the association between persistent or latent viral infections in the brain and the development of neurodegenerative diseases, offering fresh insights that could lead to new therapeutic interventions.
FIGURE 1
SARS-CoV-2 and HSV-1 Induce Amyloid Aggregation in Human CSF Resulting in Drastic Soluble Protein Depletion
Analysis Provided by Frank Bernier, PhD, MSc, CIP
With over two decades rooted in the pharmaceutical landscape, Frank’s journey has been both profound and transformative. As a seasoned professional at Eisai Co. Ltd., Japan, he donned various hats – from management to project leadership – shaping the global narrative of the company and cementing its stronghold in the Neurology sector.
Learn more about Frank Bernier, PhD, MSc, CIP here.
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